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Inhibition of amyloid-beta-induced cell death in human brain pericytes in vitro.
[hereditary cerebral hemorrhage with amyloidosis]
Amyloid-
beta
protein
(
A
beta
)
deposition
in
the
cerebral
vascular
walls
is
one
of
the
key
features
of
Alzheimer
's
disease
and
hereditary
cerebral
hemorrhage
with
amyloidosis
-
Dutch
type
(
HCHWA-D
)
.
A
beta
(
1
-
40
)
carrying
the
'
Dutch
'
mutation
(
HCHWA-D
A
beta
(
1
-
40
)
)
induces
pronounced
degeneration
of
cultured
human
brain
pericytes
.
In
this
study
,
we
aimed
to
identify
inhibitors
of
A
beta
-induced
toxicity
in
human
brain
pericytes
.
The
toxic
effect
of
HCHWA-D
A
beta
(
1
-
40
)
on
human
brain
pericytes
was
inhibited
by
co
-incubation
with
catalase
,
but
not
with
superoxide
dismutase
,
glutathione
or
vitamin
E
analogue
Trolox
.
Catalase
interacts
with
A
beta
,
both
in
cell
cultures
and
in
cell-free
assays
,
and
has
a
prominent
effect
on
the
amount
and
conformational
state
of
A
beta
binding
to
the
cell
surface
of
human
brain
pericytes
.
This
activity
of
catalase
is
likely
based
on
its
ability
to
bind
and
slowly
degrade
A
beta
and
not
by
its
usual
capacity
to
convert
hydrogen
peroxide
.
Our
data
confirm
that
assembly
of
A
beta
at
the
cell
surface
of
human
brain
pericytes
is
a
crucial
step
in
A
beta
-induced
cellular
degeneration
of
human
brain
pericytes
.
Inhibition
of
fibril
formation
at
the
cell
surface
could
be
an
important
factor
in
therapy
aimed
at
reducing
cerebral
amyloid
angiopathy
.
Diseases
Validation
Diseases presenting
"conformational state of a beta binding to the cell surface of human brain pericytes"
symptom
hereditary cerebral hemorrhage with amyloidosis
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